tbuckley/cabot-search huggingface dataset:
Rapidly adapting primary care sentinel surveillance across seven countries in Europe for COVID-19 in the first half of 2020: strengths, challenges, and lessons learned
Authors: Jayshree Bagaria, Tessa Jansen, Diogo FP Marques, Mariette Hooiveld, Jim McMenamin, Simon de Lusignan, Ana-Maria Vilcu, Adam Meijer, Ana-Paula Rodrigues, Mia Brytting, Clara Mazagatos, Jade Cogdale, Sylvie van der Werf, Frederika Dijkstra, Raquel Guiomar, Theresa Enkirch, Marta Valenciano
Journal: Eurosurveillance (2022)

As the COVID-19 pandemic began in early 2020, primary care influenza sentinel surveillance networks within the Influenza - Monitoring Vaccine Effectiveness in Europe (I-MOVE) consortium rapidly adapted to COVID-19 surveillance. This study maps system adaptations and lessons learned about aligning influenza and COVID-19 surveillance following ECDC / WHO/Europe recommendations and preparing for other diseases possibly emerging in the future. Using a qualitative approach, we describe the adaptations of seven sentinel sites in five European Union countries and the United Kingdom during the first pandemic phase (March-September 2020). Adaptations to sentinel systems were substantial (2/7 sites), moderate (2/7) or minor (3/7 sites). Most adaptations encompassed patient referral and sample collection pathways, laboratory testing and data collection. Strengths included established networks of primary care providers, highly qualified testing laboratories and stakeholder commitments. One challenge was the decreasing number of samples due to altered patient pathways. Lessons learned included flexibility establishing new routines and new laboratory testing. To enable simultaneous sentinel surveillance of influenza and COVID-19, experiences of the sentinel sites and testing infrastructure should be considered. The contradicting aims of rapid case finding and contact tracing, which are needed for control during a pandemic and regular surveillance, should be carefully balanced.
P1163: OUTCOMES OF HIGH-RISK LARGE B-CELL LYMPHOMA TREATED WITH STANDARD OF CARE CHEMOIMMUNOTHERAPY: A NON-RANDOMIZED COMPARISON TO FRONTLINE CAR-T CELL THERAPY
Authors: O. Albanyan, O. Castaneda-Puglianini, J. Chavez
Journal: HemaSphere (2022)

Background: High-risk LBCL is associated with poor prognosis after standard of care (SOC) first-line anti-CD20 mAb-containing chemoimmunotherapy (CIT), therefore here is a need for novel approaches. ZUMA-12 reported high overall response (ORR) and complete response (CR) rates in high risk LBCL defined as IPI score of ≥3 and/or double or triple-hit status [MYC and BCL2 and/or BCL6 translocations (double-hit/triple-hit lymphoma – DHL/THL)] and positive interim PET scan (iPET+) Aims: Here, we report the outcomes of these high risk LBCL patients (pts) who did not qualify due to a negative (-) iPET or declined or were ineligible to be treated in the ZUMA-12 clinical trial. Methods: Eligible patients were older than 18 and had high-risk LBCL, defined as DHL/THL status and/or an IPI score ≥3. Patients could have had an available iPET (or CT scan). Patients did not pursue ZUMA-12 due to trial ineligibility (i.e., iPET-) or did not want to pursue the trial. Patients continued SOC CIT per discretion of treating physician. The primary endpoint was end of treatment ORR and CR. Secondary endpoints included progression-free survival (PFS), overall survival (OS). Results: During the time period ZUMA-12 was open, 61 pts were approached for the trial, 8 patients were excluded from the final analysis due to incomplete data. The remaining 53 pts did not qualify to ZUMA-12 due to iPET- (n=31, 58.4%), declined (n=10, 18.8%)), ineligible (n= 8, 15.1%) and other (n= 4). Median age was 67 (26 – 78), 11 (20.1 %) had DHL/THL, 46 (86.8 %) had IPI score 3-5. Patients were treated with DA-EPOCH-R (n=11, 21%) and R-CHOP (n=41, 77%). The ORR and CR rates was 83 and 79.2%, respectively in this cohort. Four patients did not complete therapy due to PD (n=3) and death for other causes (n=1). The ORR and CR rates for the ZUMA-12 study were reported at 90 and 80%, respectively. In our study, the median PFS and OS was 27.4 months (95% CI: 23.7 – 31.1) and 30.8 months (95% CI: 27.7 – 33.8), and the 30-months PFS and OS were 60 and 71%, respectively. In comparison, the ZUMA-12 reported a PFS and OS that was not reached. Summary/Conclusion: In this nonrandomized study of high risk LBCL, the efficacy of axi-cel in the ZUMA-12 was numerically higher than SOC CIT. The PFS and OS in our cohort was lower despite majority of patients achieving early CR per iPET. This analysis supports a potential trial of frontline CAR-T versus SOC CIT for high risk LBCL.
NY-ESO-1-specific redirected T cells with endogenous TCR knockdown mediate tumor response and cytokine release syndrome
Authors: Mikiya Ishihara, Shigehisa Kitano, Shinichi Kageyama, Yoshihiro Miyahara, Noboru Yamamoto, Hidefumi Kato, Hideyuki Mishima, Hiroyoshi Hattori, Takeru Funakoshi, Takashi Kojima, Tetsuro Sasada, Eiichi Sato, Sachiko Okamoto, Daisuke Tomura, Ikuei Nukaya, Hideto Chono, Junichi Mineno, Muhammad Faris Kairi, Phuong Diem Hoang Nguyen, Yannick Simoni, Alessandra Nardin, Evan Newell, Michael Fehlings, Hiroaki Ikeda, Takashi Watanabe, Hiroshi Shiku
Journal: Journal for ImmunoTherapy of Cancer (2022)

Because of the shortage of ideal cell surface antigens, the development of T-cell receptor (TCR)-engineered T cells (TCR-T) that target intracellular antigens such as NY-ESO-1 is a promising approach for treating patients with solid tumors. However, endogenous TCRs in vector-transduced T cells have been suggested to impair cell-surface expression of transduced TCR while generating mispaired TCRs that can become self-reactive.
P639: OUTCOMES FOR PATIENTS WITH CHRONIC LYMPHOCYTIC LEUKEMIA PREVIOUSLY TREATED WITH A COVALENT BTK AND BCL2 INHIBITOR IN THE UNITED STATES: A REAL-WORLD DATABASE STUDY
Authors: A. R. Mato, Y. Chen, A. C. Girvan, L. M. Hess, L. Bowman, P. Abada, H. Konig, R. A. Walgren
Journal: HemaSphere (2022)

Background: Covalent BTK inhibitors (cBTK) and B-cell lymphoma 2 inhibitors (BCL2i) have transformed outcomes in patients with chronic lymphocytic leukemia (CLL). Although these agents are highly effective, they are not curative, and a proportion of patients will require additional therapy. No prospective randomized clinical trials have evaluated the efficacy of therapies following treatment with these two modern drug classes. Aims: We therefore evaluated treatment outcomes in patients with CLL following treatment with at least these two drug classes using a real-world dataset from the United States (US). Methods: De-identified patient-level electronic medical record data linked to claims data in the US from ConcertAI were utilized for this study. Eligible patients were ≥18 years old, diagnosed with CLL between December 2011 and October 2020. To ensure a minimum of 1 year follow-up for all patients, data were available through July 2021. Patients were required to have completed treatment with at least one cBTKi and a BCL2i during the 1st-3rd lines of therapy. Time-to-event analyses utilized the Kaplan-Meier method. Results: 382 patients (median age 73.4 years, male 64.4%) met eligibility criteria. Of these, 228 (59.7%) received subsequent therapy following BTK inhibitor and BCL2 inhibitor regimens, while the remaining 154 (40.3%) did not receive further treatment. Among those who received further treatment, the most common therapies included retreatment with a venetoclax-containing regimen (n=112, 49.1%). Of note, only 2.6% (n=6) of patients received immediate post-dual failure therapy with a PI3K inhibitor in this setting. Among those who received subsequent therapy (n=228), the median time from the start of the immediate post-cBTKi/BCL2i therapy to discontinuation or death was 5.5 months (95% CI: 3.5-6.9). For the entire cohort of patients with CLL who discontinued BTKi and BCL2i regimens (n=382), the median time from the end of the last of BTKi/BCL2i therapy to discontinuation of subsequent therapy or death was 5.6 months (95% CI: 4.3-6.0). Summary/Conclusion: Patients with CLL who have been previously treated with both a cBTKi and BCL2i experience poor outcomes as observed by duration of treatment and time to treatment discontinuation of subsequent therapy. This population represents a growing area of unmet medical need for patients with CLL.
Complement C3a and C3a Receptor Activation Mediates Podocyte Injuries in the Mechanism of Primary Membranous Nephropathy
Authors: Shuang Gao, Zhao Cui, Ming-hui Zhao
Journal: Journal of the American Society of Nephrology (2022)

The complement system is highly activated in primary membranous nephropathy (MN). Identifying the complement components that damage podocytes has important therapeutic implications. This study investigated the role of C3a and the C3a receptor (C3aR) in the pathogenesis of MN. C3aR expression in kidneys and circulating levels of C3a of MN patients were examined. Human podocyte damage was assessed after exposure to MN plasma +/- C3aR blockade (SB290157, JR14a). C3aR antagonists were administered to rats with Heymann nephritis on day 0 or after proteinuria. Clinical and pathologic parameters, specific IgG and complement activation, and podocyte injuries were then assessed. In the glomeruli, C3aR staining merged well with podocin. Overexpression of C3aR correlated positively with proteinuria, serum creatinine, and no response to treatments. Human podocytes exposed to MN plasma showed increased expression of PLA2R, C3aR, and Wnt3/β-catenin, reduced expression of synaptopodin and migration function, downregulated Bcl-2, and decreased cell viability. C3aR antagonists could block these effects. In Heymann nephritis rats, C3aR blockade attenuated proteinuria, electron-dense deposition, foot process width, and glomerular basement membrane thickening in glomeruli. The increased plasma C3a levels and overexpression of C3aR were also alleviated. Specific, but not total, IgG levels decreased, with less deposition of rat IgG in glomeruli and subsequent reduction of C1q, factor B, and C5b-9. C3a anaphylatoxin is a crucial effector of complement-mediated podocyte damage in MN. The C3aR antagonist may be a potentially viable treatment for this disease.
Correction: A Phase I Study of an MPS1 Inhibitor (BAY 1217389) in Combination with Paclitaxel Using a Novel Randomized Continual Reassessment Method for Dose Escalation
Authors: Florence Atrafi, Oliver Boix, Vivek Subbiah, Jennifer R. Diamond, Sant P. Chawla, Anthony W. Tolcher, Patricia M. LoRusso, Joseph P. Eder, Martin Gutierrez, Kumar Sankhala, Prabhu Rajagopalan, Isabelle Genvresse, Simon Langer, Ron H.J. Mathijssen, Jaap Verweij, Ingmar Bruns, Martijn P. Lolkema
Journal: Clinical Cancer Research (2022)

In the original version of this article (1), errors exist in Tables 2, 3, and 4 and in the Results section. In Table 2, the bioavailability factor was listed for the oral solution instead of the liquid capsule formulation, which has a lower bioavailability of 38%, and thus the bioavailability factor in footnote “a” should list 2.6 instead of 2.7; also in Table 2, all five 90% credible interval values are for the oral solution instead of the liquid capsule formulation and should have been adjusted accordingly. In the Results section and in Table 3’s footnote “a”, the bioavailability of liquid capsule formation should be 38% instead of –31%. In Table 4, the 40% value for the Median MTD in mg for rCRM-20 should be 7.4 instead of 53.2. The errors have been corrected in the latest online HTML and PDF versions of the article. The authors regret the errors.
Guanylated Hyperbranched Polylysines with High In Vitro and In Vivo Antifungal Activity
Authors: Xiao Liu, Yilong Yang, Miaomiao Han, Jianwei Guo, Hui Liu, Yadong Liu, Junjie Xu, Shengxiang Ji, Xuesi Chen
Journal: Advanced Healthcare Materials (2022)

Abstract With the rapid growth of fungal infections and the emergence of multi‐drug resistant (MDR) fungal strains, new antifungals with novel mechanisms are a pressing need to tackle this emerging health problem. Herein it is reported for the first time that hyperbranched polylysine (HPL) shows antifungal activities against Candida , especially for drug‐sensitive and MDR C. albicans strains, and broad‐spectrum antibacterial activities against both Gram‐negative and Gram‐positive bacteria. The high antimicrobial activities are ascribed to the high charge density and compact size of the globular structure of HPL. The in vitro antifungal activities of HPL3 are further enhanced by the modification of amine groups to form guanylated polylysines (HPL3‐Gxs). Similar to antimicrobial peptides (AMPs), HPLs and HPL3‐Gxs interact with and lyse the membranes of microbes, which mitigates the emergence of drug resistance. HPLs and HPL3‐Gxs demonstrate excellent in vivo antimicrobial efficacies against both lethal C. albicans challenge in the invasive candidiasis model and lethal Methicillin resistant Staphylococcus aureus challenge in the peritonitis model, and have potentials as broad‐spectrum antimicrobials.
Dostarlimab: An Answer for Rectal Cancer?
Journal: Cancer Discovery (2022)

Abstract In a phase II study testing the PD-1 inhibitor dostarlimab in locally advanced mismatch repair–deficient rectal cancer, 100% of evaluable patients experienced a clinical complete response without needing other therapies. Standard treatment for the disease, which includes chemotherapy, radiation therapy, and surgery, can lead to bowel, urinary, and sexual dysfunction, infertility, and permanent ostomy, but the study's findings suggest that neoadjuvant checkpoint blockade could spare patients these life-altering adverse events.
World Bronchiectasis Day 2022
Authors: James D. Chalmers, Timothy Aksamit, Stefano Aliberti, Raja Dhar, Lucy C. Morgan
Journal: European Respiratory Journal (2022)

On 1 July 2022 we celebrate the first World Bronchiectasis Day. The day is an opportunity to raise awareness of the disease globally, provide information and support to patients, and to promote improved clinical services and more research into this neglected disease. International organisations come together to raise awareness of bronchiectasis on 1 July 2022: World Bronchiectasis Day https://bit.ly/3tPH7EU World Bronchiectasis Day is supported by the US COPD Foundation, the American Thoracic Society, EMBARC: the European Bronchiectasis Network, the European Lung Foundation, NTM Information and Research, the Lung Foundation of Australia, the American Lung Association, Lovexair Foundation, the Japanese Respiratory Society, the Chinese Thoracic Society, Global Allergy and Airways Patient Platform, the Indian Chest Society, the American College of Chest Physicians, the American Association for Respiratory Care, the South African Thoracic Society, the US COPD Coalition, Running on Air and the Cystic Fibrosis Foundation.
Risk and severity of SARS-CoV-2 reinfections during 2020–2022 in Vojvodina, Serbia: A population-level observational study
Authors: Snežana Medić, Cleo Anastassopoulou, Zagorka Lozanov-Crvenković, Vladimir Vuković, Nataša Dragnić, Vladimir Petrović, Mioljub Ristić, Tatjana Pustahija, Zoran Gojković, Athanasios Tsakris, John P.A. Ioannidis
Journal: The Lancet Regional Health - Europe (2022)
The Cost of Control: Cost-effectiveness Analysis of Hybrid Closed-Loop Therapy in Youth
Authors: Anthony Pease, Emily Callander, Ella Zomer, Mary B. Abraham, Elizabeth A. Davis, Timothy W. Jones, Danny Liew, Sophia Zoungas
Journal: Diabetes Care (2022)

Hybrid closed-loop (HCL) therapy is an efficacious management strategy for young people with type 1 diabetes. However, high costs prevent equitable access. We thus sought to evaluate the cost-effectiveness of HCL therapy compared with current care among young people with type 1 diabetes in Australia.A patient-level Markov model was constructed to simulate disease progression for young people with type 1 diabetes using HCL therapy versus current care, with follow-up from 12 until 25 years of age. Downstream health and economic consequences were compared via decision analysis. Treatment effects and proportions using different technologies to define "current care" were based primarily on data from an Australian pediatric randomized controlled trial. Transition probabilities and utilities for health states were sourced from published studies. Costs were considered from the Australian health care system's perspective. An annual discount rate of 5% was applied to future costs and outcomes. Uncertainty was evaluated with probabilistic and deterministic sensitivity analyses.Use of HCL therapy resulted in an incremental cost-effectiveness ratio of Australian dollars (AUD) $32,789 per quality-adjusted life year (QALY) gained. The majority of simulations (93.3%) were below the commonly accepted willingness-to-pay threshold of AUD $50,000 per QALY gained in Australia. Sensitivity analyses indicated that the base-case results were robust.In this first cost-effectiveness analysis of HCL technologies for the management of young people with type 1 diabetes, HCL therapy was found to be cost-effective compared with current care in Australia.
Role of Magnetic Resonance Cholangiopancreatography in the Diagnosis of Cystic Transformation Hepaticocholedoch and Possible Postoperative Complications (Clinical Case)
Authors: O. V. Lukovkina, N. A. Sholohova, Yu. Yu. Sokolov, T. V. Utkina
Journal: Radiology - Practice (2022)

The article presents a description of a clinical case in a 7-year old child suffering occasional abdominal pain. An examination (3D magnetic resonance cholangiopancreatography) revealed a choledoch duct cyst type Iс. Surgical correction of congenital malformation of bile ducts was performed due to periodic attacks of pain, presence of concretions in the ducts, the possibility of malignification in the future and the development of possible complications. The clinical example demonstrates the high efficiency of MRCP for assessing anatomical and topographic relationships and concomitant structural anomalies that allow planning the tactics of surgical treatment. MRCP is important to use in the postoperative period to assess possible complications.
Sympatric Recombination in Zoonotic Cryptosporidium Leads to Emergence of Populations with Modified Host Preference
Authors: Tianpeng Wang, Yaqiong Guo, Dawn M Roellig, Na Li, Mónica Santín, Jason Lombard, Martin Kváč, Doaa Naguib, Ziding Zhang, Yaoyu Feng, Lihua Xiao
Journal: Molecular Biology and Evolution (2022)

Abstract Genetic recombination plays a critical role in the emergence of pathogens with phenotypes such as drug resistance, virulence, and host adaptation. Here, we tested the hypothesis that recombination between sympatric ancestral populations leads to the emergence of divergent variants of the zoonotic parasite Cryptosporidium parvum with modified host ranges. Comparative genomic analyses of 101 isolates have identified seven subpopulations isolated by distance. They appear to be descendants of two ancestral populations, IIa in northwestern Europe and IId from southwestern Asia. Sympatric recombination in areas with both ancestral subtypes and subsequent selective sweeps have led to the emergence of new subpopulations with mosaic genomes and modified host preference. Subtelomeric genes could be involved in the adaptive selection of subpopulations, while copy number variations of genes encoding invasion-associated proteins are potentially associated with modified host ranges. These observations reveal ancestral origins of zoonotic C. parvum and suggest that pathogen import through modern animal farming might promote the emergence of divergent subpopulations of C. parvum with modified host preference.
Impact of demographic changes and screening colonoscopy on long-term projection of incident colorectal cancer cases in Germany: A modelling study
Authors: Thomas Heisser, Michael Hoffmeister, Hanna Tillmanns, Hermann Brenner
Journal: The Lancet Regional Health - Europe (2022)

Demographic aging is expected to increase the number of colorectal cancer (CRC) cases in many countries. Screening for CRC can substantially reduce the disease burden but its use has remained rather limited in Germany. We aimed to quantify the expected impact of demographic aging on the future CRC burden and the potential to reduce that burden by increased use of screening colonoscopy offers in Germany.
Assessment of Resilience Training for Hospital Employees in the Era of COVID-19
Authors: Joyce P. Yi-Frazier, Maeve B. O’Donnell, Elizabeth A. Adhikari, Chuan Zhou, Miranda C. Bradford, Samantha Garcia-Perez, Kelly J. Shipman, Samantha E. Hurtado, Courtney C. Junkins, Alison O’Daffer, Abby R. Rosenberg
Journal: JAMA Network Open (2022)

<h3>Importance</h3> Health care workers face serious mental health challenges as a result of ongoing work stress. The COVID-19 pandemic exacerbated that stress, resulting in high rates of anxiety, depression, and burnout. To date, few evidence-based programs targeting mental health outcomes in health care workers have been described. <h3>Objective</h3> To assess the feasibility, acceptability, and preliminary outcomes of a skills-based coaching program designed to reduce stress and build resilience. <h3>Design, Setting, and Participants</h3> A pilot cohort study was conducted between September 2020 and April 2021 using preprogram and postprogram assessments and a mixed-methods analysis. Duration of follow-up was 7 weeks. The coaching program was delivered via video conferencing. Participants were health care workers and staff from a large urban health system. <h3>Intervention</h3> The Promoting Resilience in Stress Management (PRISM) program, a manualized, skills-based coaching program originally developed for adolescents and young adults with serious/chronic illness, was adapted to support health care workers and staff ("PRISM at Work"). It included 6 weekly 1-hour group sessions. <h3>Main Outcomes and Measures</h3> Feasibility was defined a priori as 70% completion rates. Acceptability was defined quantitatively (satisfaction scores) and qualitatively (open-ended questions regarding experience with program). Preliminary outcomes were assessed with preprogram and post program assessments of self-reported resilience, stress, anxiety, and burnout using validated instruments. Descriptive statistics summarized demographic variables and feasibility and acceptability. Linear mixed effects regression models examined preliminary outcomes, controlling for relevant covariates. <h3>Results</h3> A total of 153 participants (median [SD] age, 40.6 [10.1] years; 142 [92%] were female; 128 [84%] identified as having White race; 81 [53%] were in patient-facing roles) enrolled. Of the 132 health care workers who provided follow-up surveys, 120 (91%) had completed the program, and 116 (88%) reported being satisfied. Answers to open-ended questions suggested that participants wanted more PRISM either with longer or additional sessions. Participant-reported resilience (β = 1.74; 95% CI, 1.00-2.48), stress (β = −2.40; 95% CI, −3.28 to −1.51), anxiety (β = −2.04; 95% CI, −2.74 to −1.34), and burnout-exhaustion (β = −0.37; 95% CI, −0.56 to −0.18) improved after the program. <h3>Conclusions and Relevance</h3> Results of this study suggest that PRISM at Work may have utility for health care workers and staff in that the program was found to be feasible, acceptable, and associated with improved outcomes.